Project Summary/Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. Since early detection of CRC is associated with excellent survival rates, development of non- invasive and highly reliable test for CRC is greatly needed for veterans. While colonoscopy has reported sensitivity and specificity values exceeding 95%, the degree of adherence is low due to the cost, as well as to perceived inconvenience and discomfort associated with this test. As a result, many patients still present with late-stage and potentially fatal disease. We have found that plasma levels of several lipids, called lysophosphatidylcholines (LPCs), are potential markers for CRC and our pilot work show that these markers achieved a sensitivity and specificity of 82% and 93%, respectively for CRC. It is critical and absolutely necessary to establish reproducibility and to retest and validate the estimates for sensitivity and specificity in completely independent VA population sets in order to critically evaluate the clinical significance and utility of these markers to be useful for veterans. We propose 2 aims. First, we will critically evaluate whether plasma LPC levels are effective markers for detecting CRC by determining their sensitivity and specificity in VA patient population, a totally independent study population. Secondly, we will determine whether plasma LPC levels are effective markers for pre-cancerous adenomatous colon polyps. Our long-term goals are 1) to develop highly sensitive and reliable diagnostic and prognostic, non- or minimally invasive biomarkers for improving early detection, management and follow up of CRC patient samples obtained and 2) to develop biomarkers to detect pre-cancerous adenomatous colon polyps. Potential Impact on Veterans Health Care: More veterans are diagnosed and/or treated for colorectal cancer in the Veteran Administration (VA) and such CRC incidence rate will increase with aging VA population. The proposed research will provide an important diagnostic non-invasive tool for veterans to improve early detection of CRC and colon polyp thus optimize CRC medical care for VA population. PUBLIC HEALTH RELEVANCE: Potential Impact on Veterans Health Care: More veterans are diagnosed and/or treated for colorectal cancer in the Veteran Administration (VA) and such CRC incidence rate will increase with aging VA population. The proposed research will provide an important diagnostic non-invasive tool for veterans to improve early detection of CRC and colon polyp thus optimize CRC medical care for VA population.